Identification of morphological markers of sarcopenia at early stage of aging in skeletal muscle of mice

Sayed, Ramy K. A.; Leonardis, Erika Chacin de; Guerrero-Martínez, José A.; Rahim, Ibtissem; Mokhtar, Doaa M.; Saleh, Abdelmohaimen M.; Abdalla, Kamal E. H.; Pozo, Marı́a J.; Escames, Germaine; López, Luís C.; Acuña-Castroviejo, Darı́o

doi:10.1016/j.exger.2016.07.007

Cited by 57 publications

(48 citation statements)

References 55 publications

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“…Aging-related skeletal muscle atrophy is known not only to accelerate the loss of skeletal muscle fiber and strength, but also to be associated with mobility impairment, an increased risk of falls, and physical frailty [36]. The analysis for the impact of aging on the internal structure of skeletal muscle fibers indicates that Type II fiber atrophy is an early contributor to aging-related muscle atrophy [37]. Therefore, gastrocnemius muscle is chosen as the object in the present study.…”

Section: Discussionmentioning

confidence: 99%

Spermidine coupled with exercise rescues skeletal muscle atrophy from D-gal-induced aging rats through enhanced autophagy and reduced apoptosis via AMPK-FOXO3a signal pathway

et al. 2017

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The quality control of skeletal muscle is a continuous requirement throughout the lifetime, although its functions and quality present as a declining trend during aging process. Dysfunctional or deficient autophagy and excessive apoptosis may contribute to the atrophy of senescent skeletal muscle. Spermidine, as a natural polyamine, can be involved in important cellular functions for lifespan extension and stress resistance in several model organisms through activating autophagy. Similarly, cellular autophagic responses to exercise have also been extensively investigated. In the present study, in order to confirm the mitigation or amelioration of skeletal muscle atrophy in aging rats through spermidine coupled with exercise intervention and explore corresponding mechanisms, the rat model with aging-related atrophy of skeletal muscle was established by intraperitoneal injection of D-galactose (D-gal) (200 mg/kgd), and model rats were subjected to the intervention with spermidine (5 mg/kgd) or swimming (60 min/d, 5 d/wk) or combination for 42 days. Spermidine coupled with exercise could attenuate D-gal-induced aging-related atrophy of skeletal muscle through induced autophagy and reduced apoptosis with characteristics of more autophagosomes, activated mitophagy, enhanced mitochondrial quality, alleviated cell shrinkage, and less swollen mitochondria under transmission scanning microscopic observation. Meanwhile, spermidine coupled with exercise could induce autophagy through activating AMPK-FOXO3a signal pathway with characterization of increased Beclin1 and LC3-II/LC3-I ratio, up-regulated anti-apoptotic Bcl-2, down-regulated pro-apoptotic Bax and caspase-3, as well as activated AMPK and FOXO3a. Therefore, spermidine combined with exercise can execute the prevention or treatment of D-gal-induced aging-related skeletal muscle atrophy through enhanced autophagy and reduced apoptosis mediated by AMPK-FOXO3a signal pathway.

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Section: Discussionmentioning

confidence: 99%

Spermidine coupled with exercise rescues skeletal muscle atrophy from D-gal-induced aging rats through enhanced autophagy and reduced apoptosis via AMPK-FOXO3a signal pathway

et al. 2017

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“…1a and e). Fibroblasts were derived from arm and abdomen skin biopsies (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) years for the young control, n=3, and 60-70 years for the aged group, n= 3), while endothelial cells were extracted from iliac vein and artery (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) years for the young control, n=3, and 45-50 years for the aged group, n=3). We utilized a non-integrative reprogramming protocol that we optimized, based on a cocktail of mRNAs expressing OCT4, SOX2, KLF4, c-MYC, LIN28 and NANOG (OSKMLN) 11 .…”

Section: Mainmentioning

confidence: 99%

“…Sarcopenia is an age-related condition that is characterized by loss of muscle mass and force production 32,33 . Similarly, in mice muscle functions show progressive degeneration with age 34,35 .We wanted to test whether transient reprogramming of aged MuSCs would improve a cell-based treatment in restoring physiological functions of muscle of older mice. To test this, we first performed electrophysiology to measure tetanic force production in TA muscles isolated from young (4 months) or aged (27 months) immunocompromised mice.…”

Section: Mainmentioning

confidence: 99%

Transient non-integrative nuclear reprogramming promotes multifaceted reversal of aging in human cells

Quarta

Mukherjee

et al. 2019

Preprint

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Aging is characterized by a gradual loss of function occurring at the molecular, cellular, tissue and organismal levels [1][2][3] . At the chromatin level, aging is associated with the progressive accumulation of epigenetic errors that eventually lead to aberrant gene regulation, stem cell exhaustion, senescence, and deregulated cell/tissue homeostasis 3 . The technology of nuclear reprogramming to pluripotency, through over-expression of a small number of transcription factors, can revert both the age and the identity of any cell to that of an embryonic cell by driving epigenetic reprogramming 2,4,5 . Recent evidence has shown that transient transgenic reprogramming can ameliorate age-associated hallmarks and extend lifespan in progeroid mice 6 .However, it is unknown how this form of 'epigenetic rejuvenation' would apply to physiologically aged cells and, importantly, how it might translate to human cells. Here we show that transient reprogramming, mediated by transient expression of mRNAs, promotes a rapid reversal of both cellular aging and of epigenetic clock in human fibroblasts and endothelial cells, reduces the inflammatory profile in human chondrocytes, and restores youthful regenerative response to aged, human muscle stem cells, in each case without abolishing cellular identity. Our method, that we named Epigenetic Reprogramming of Aging (ERA), paves the way to a novel, potentially translatable strategy for ex vivo cell rejuvenation treatment. In addition, ERA holds promise for in vivo tissue rejuvenation therapies to reverse the physiological manifestations of aging and the risk for the development of age-related diseases.

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“…In order to improve the robustness, especially for cases where the endomysium region, i.e. the region between two cells [9], is not clear, we combine the pixel-wise classification with the Ultrametric Contour Maps ( UCM ) [28]. …”

Section: Muscle Cell Segmentationmentioning

confidence: 99%

“…However, the efficient CBIR system for CAD relies on the efficient representation of the images [8], and the prerequisite is to identify the clinically significant image markers. Therefore, we propose an IIM CAD system with an entire pipeline comprised of following three steps: 1) Skeletal muscle image marker (illustrated in Figure 1(a)) identification, which contains muscle fiber (individual contractile units in the muscle) segmentation, perimysium (dense collagen between bundles of muscle fibers [9]) annotation, and nucleus (relatively smaller and elongated or oval structure normally inside muscle fiber) center detection; 2) Muscle image feature extraction, which includes computing the cross section area ( CSA ) of muscle fibers and the physical distribution of nuclei centers; 3) Automatic IIM diagnosis, which involves the establishment of an entire muscle image CBIR module. In the past few decades, although lots of CAD systems have been developed to process and diagnose different radiology and pathology images [10], [11], to the best of our knowledge, this is the first CAD system to process IIM image data.…”

Section: Introductionmentioning

confidence: 99%

AIIMDs: An Integrated Framework of Automatic Idiopathic Inflammatory Myopathy Diagnosis for Muscle

Sapkota

Liu

Xie

et al. 2018

IEEE J. Biomed. Health Inform.

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Idiopathic Inflammatory Myopathy (IIM) is a common skeletal muscle disease that relates to weakness and inflammation of muscle. Early diagnosis and prognosis of different types of IIMs will guide the effective treatment. Interpretation of digitized images of the cross section muscle biopsy, which is currently done manually, provides the most reliable diagnostic information. With the increasing volume of images, the management and manual interpretation of the digitized muscle images suffer from low efficiency and high interobserver variabilities. In order to address these problems, we propose the first complete framework of automatic IIM diagnosis system (AIIMDs) for the management and interpretation of digitized skeletal muscle histopathology images. The proposed framework consists of several key components: (1) Automatic cell segmentation, perimysium annotation, and nuclei detection; (2) Histogram based feature extraction and quantification; (3) Content-based image retrieval (CBIR) to search and retrieve similar cases in the database for comparative study; and (4) Majority voting based classification to provide decision support for computer aided clinical diagnosis. Experiments show that the proposed diagnosis system provides efficient and robust interpretation of the digitized muscle image and computer aided diagnosis of IIM.

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Identification of morphological markers of sarcopenia at early stage of aging in skeletal muscle of mice

Cited by 57 publications

References 55 publications

Spermidine coupled with exercise rescues skeletal muscle atrophy from D-gal-induced aging rats through enhanced autophagy and reduced apoptosis via AMPK-FOXO3a signal pathway

Spermidine coupled with exercise rescues skeletal muscle atrophy from D-gal-induced aging rats through enhanced autophagy and reduced apoptosis via AMPK-FOXO3a signal pathway

Transient non-integrative nuclear reprogramming promotes multifaceted reversal of aging in human cells

AIIMDs: An Integrated Framework of Automatic Idiopathic Inflammatory Myopathy Diagnosis for Muscle

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